Blood purification in sepsis Joannes-Boyau O Dept of anesthesiology and intensive care, University Hospital of Bordeaux, France 1
Types of Blood Purification hemofilters regular pore size (MW < 40,000D) Low flux High flux large pore filtration (MW < 100,000D) open pore plasma filters plasma exchange Plasmapheresis adsorption coupled plasma filtration / adsorption
Plasmafiltration Blood pump Plasma Veno-venous catheter Plasmafilter Substitute Plasma colloids
Cascade filtration
CPFA
Sepsis
Interest of CRRT Renal replacement therapy Regulation of electrolyte, acid-base equilibration Volume balance, avoid volume overload Removal of immunological and biological active molecules, re-establish of immune homeostasis Regulation of body temperature
Immuno-modulation concept Non-selective removal of cytokines by hemofiltration Equilibration between pro- and antiinflammatory cytokines and mediators Down-regulation Skerrett S.J. et al. Journal of Infectious Diseases. 1997 Kellum J et al. Crit Care med. 1998 Kellum J et al. Minerva Anesthesiol. 1999
Peak-Concentration Hypothesis Ronco C, et al. Artif Organs. 2003
Plasmapheresis: Clinical Studies ANIMAL STUDIES Author Results Reference Busund 91 Natanson 93 no survival advantage Arch Surg no survival advantage Transfusion HUMAN STUDIES Author Type of Study Results Reference Van Deuren 92 observational no benefit Clin Infect Dis Reeves 95 retrospective no benefit Int Care Med Berlot 97 observational no benefit Blood Purif Kumar 98 observational no benefit Nephrol Dial Trans Reeves 99 RCT no benefit Crit Care Med Schmidt 2000 observational no benefit Int Care Med
Plasmapheresis Conventional
CPFA
CPFA: Experimental Studies In-Vitro studies much more efficient clearance of cytokines Animal Studies rabbit model of LPS septic shock (Tetta C, Crit Care Med 2000) 85% survival in rabbits supported with CPFA 80% mortality in control rabbits Human Clinical Study (Brendolan A, J Am Soc Nephrol 1998) improved hemodynamics SVR reduced inotrope requirements improved monocyte responsiveness
New filtration techniques : PFAD (Plasma filtration adsorption dialysis) Dialysis with patient s regenerated plasma Tricompartimental dialyser Plasma depuration Plasma / dialysate Adsorption Plasma reinfused Nalesso. F, IJAO 2005
NFκB removal from Liver 16
Grootendorst AF. J Crit Care 1993 Healthy pigs No effect SVRi + CO Septic Pigs Sepsis like 17
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Survival (%) 60 50 P < 0,0016 40 30 * 20 10 0 20 ml/kg/hr 35 ml/kg/hr 45 ml/kg/hr Ultrafiltration rate 19
20 patients, Refractory septic shock PAM 55 mm Hg, IC 2,5 l/mn/m 2, catécho doses max., PAPO 16 mmhg, SvO2 55 %, ph 7,15, lactates 5mmol/l, PaO2/FiO2 100 4 h HFHV (9l/h) isovolumic + 4 days (minimum) of CVVH Responders Non Responders CI 50 % H2, SVO2 25 % H2 ph > 7.30 H4, Adré 50 % H4 20
Predictable Mortality : 79 % Observed Mortality : Global patients : 55 % Responders : 18,1 % Non responders : 100 % Survival associated factors Weight and real UF (0,53 vs 0,43 l/kg) Start time : 6,5 h (3,25-12) vs 13,8 h (9,6-17,5) p 0,01 21
SAP (mmhg) ND (µg/kg/mn) CI (L/mn/m²) 130 5 120 110 100 90 80 70 60 * * * * * * 4,5 4 3,5 3 2,5 2 1,5 1 0,5 Systolic blood pressure (SAP) Cardiac index (CI) norepinephrine doses (ND) 50 0 Time (Hour) 22
With HVHF we can see : Increase of Hemodynamics parameters Important decrease of catecholamines doses Observed Mortality 46% VS Predictable Mortality 70% (p<0,075) 23
Intensive Care Med. 2006 Mar 21 24
Intensive Care Med. 2006 Mar 21 Increase of Hemodynamics parameters Important decrease of catecholamines doses Observed Mortality 40% VS Predictable Mortality 63% (p<0,03) Responders 18% Vs Non Responders 67% 25
- 19 patients Randomized - 35 ml/kg/h Vs 65 ml/kg/h during 4 days. - Global mortality at D28 = 47% - Specific mortality : LVH = 50% vs HVH = 44% 26
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Future? 31
«IVOIRE study» high VOlume in Intensive care Prospective randomized multinational simple blind study evaluating the adequate dose of continuous high volume haemofiltration in the early treatment «phase» of Septic Shock patients with Acute Renal Failure. Should defined the adequate «Septic Dose» of CRRT during Septic Acute Renal Failure in ICU. 32
«IVOIRE study» 420 139 patients with Septic Shock and Acute Renal Failure Randomization within 24 hours of ICU admission (! Early septic shock) Any dose of vasopressors (Noradrenaline) Or > 5µg/kg/m of Dopamine - Oliguria < 0.5 ml/kg/h - creatinine X 2 RIFLE Injury 35 ml/kg/h 70 ml/kg/h Mortality D28 D90 33
The Dark Side 34 34
The Depletion syndrome Albumin (Carriers) Drugs Antibiotics Catecholamines Microconutrients Energy Macronutrients Trace Elements Hydrosolubles Vitamines Amino-Acids Frankenfield et al. Nutrition 1995;11:388-393 35
RIFLE Criteria Risk Injury GFR Criteria Increased creatinine x1.5 or GFR decrease > 25% Increased creatinine x2 or GFR decrease > 50% Urine Output Criteria UO <.5ml/kg/h x 6 hr UO <.5ml/kg/h x 12 hr High Sensitivity Failure Loss ESKD Increase creatinine x3 or GFR decrease > 75% End Stage Kidney Disease (> 3 months) UO <.3ml/kg/h x 24 hr or Anuria x 12 hrs Persistent ARF** = complete loss of kidney function > 4 weeks High Specificity
Early HF Control 37
Timing of Renal Replacement Therapy Initiation in Acute Renal Failure: A Meta-analysis Seabra VF et al. Am J Kidney Dis 2008; 52: 272-84 Effect on mortality 38
Timing of Renal Replacement Therapy Initiation in Acute Renal Failure: A Meta-analysis Seabra VF et al. Am J Kidney Dis 2008; 52: 272-84 Effect on renal recovery 39
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Summary Very interesting techniques in septic patients Immuno-modulator effect and homeostasis recovery Maximum effect with high volume and fast start Some place for plasmafiltration but Adsorption the missing piece? But : Depletion syndrome Some technical problems What do we use? (continuous, intermittent, volume, etc...) 48